In adults, growth factors and their binding proteins influence bone formation, and the cytokine IL-6 promotes osteoclast recruitment and bone resorption. The primary aims of this proposed supplement to our STOP/IT continuation study are to determine whether supplementation with calcium and vitamin D changes circulating levels of IGF-1, IGFBP-4, and IL-6 and, if so, whether changes in circulating levels of these compounds are associated with the beneficial effect of supplementation on rates of bone loss. This study tests the hypothesis that supplemental calcium and vitamin D, by lowering circulating levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D), will a) decrease the IGFBP-4 medicated inhibition of IGF-1 induced bone formation and b) decrease IL-6 induced bone resorption. At Tufts, 389 adults over age 65 (172 men and 273 women) recently completed a 3-year, randomized, double-blind controlled trial designed to determine whether calcium and vitamin D supplementation reduced rates of bone loss from the total body, hip, and spine. Subjects received either 500mg of calcium plus 700 IU of vitamin D or placebo daily. Bone mineral density and calcium regulating hormone levels and other biochemistries were followed. During the trial, supplementation significantly lowered circulating levels of PTH and 1,25(OH)2D and reduced rates of bone loss from each skeletal site. The proposed study involves assaying archived Tufts STOP/IT samples collected at baseline and after three years of treatment for IGF-1, IGFBP-4, and IL-6. With the addition of these measurements, the STOP/IT data set would offer an enriched opportunity to explore potential mechanisms by which changes in calcium and vitamin D intake influence rates of bone loss.